Mitochondrially targeted antioxidants have been shown to modestly slow aging in a number of short-lived laboratory species, a smaller effect than that of calorie restriction. They have larger effects on inflammatory conditions, however, which is why the present thrust of clinical development is focused on a number of inflammatory eye conditions. This is in contrast to the sort of antioxidants you can buy in a supplement store, which do nothing useful, and at higher doses even appear to harm long-term health by interfering in signaling that mediates the beneficial response to exercise. Altered levels of mitochondrially generated oxidants show up in a range of methods that alter the pace of aging in animal species, mostly based on genetic engineering to alter mitochondrial operations. Here researchers are developing a drug-based approach along the same lines:
Go to any health food store and you're likely to see shelves crowded with antioxidants that promise to quell damage from free radicals, which are implicated in a myriad of human diseases and in the aging process itself. The problem is that antioxidants have failed to show benefits in several clinical trials and there is even some evidence they could be counterproductive. The current approaches to free radicals may fail because they apply a "sledgehammer" to a complex metabolic process that provides essential energy to our cells. Free radicals are produced in the mitochondria - the energy-converting organelles which are abundant in almost every type of human cell. Highly-reactive free radicals, which oxidize cell constituents (hence the use of antioxidants), are spun-off as a normal byproduct of cellular bioenergetics; it's a process that appears to go up when cells are stressed, something that can occur with aging and disease.
A chain of electron transporters within the mitochondria is involved in the production of both free radicals and the chemical energy essential for life. The challenge has been to stop the free radicals without shutting down the cell's ability to release energy. Researchers did that by painstakingly screening 635,000 small molecules to single out the few that blocked free radical production at a specific site thought to be a major source of free radicals in the electron transport chain. In this latest research, they demonstrated the potency and specificity of the successful molecules and tested their effects in cell culture, isolated hearts, and live models of disease. The compounds dramatically protected against reperfusion injury in a mouse heart model of ischemia. "Most of the lasting damage from heart attacks comes when blood flow is restored to the heart muscle. These compounds have great potential as therapeutic leads for drugs that could be given following a heart attack or after stents have been inserted to open blocked coronary blood vessels." In addition, the molecules diminished oxidative damage in brain cells cultured in low levels of oxygen; they also diminished stem cell hyperplasia in the intestines of fruit flies.
The study offers researchers a way to test the hypothesis that oxidative damage is specifically linked to disease. "For the first time we can test the effects of free radical damage in Alzheimer's, Parkinson's, cancer, type 2 diabetes, macular degeneration - you name it. It gives you a target, and a drug candidate to hit that target. We can start to answer questions that scientists have puzzled about for 50 years in terms of the specifics of oxidative damage. We now have a precise tool to find out if the theory is correct. We can go into a biological system, see specifically what free radicals do and take preliminary steps to stop it."